[Federal Register Volume 84, Number 63 (Tuesday, April 2, 2019)]
[Proposed Rules]
[Pages 12534-12537]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-06188]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 610

[Docket No. FDA-2018-N-4757]
RIN 0910-AH95


Revocation of the Test for Mycoplasma

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
proposing to amend the biologics regulations by removing the specified 
test for the presence of Mycoplasma for live virus vaccines and 
inactivated virus vaccines produced from in vitro living cell cultures. 
FDA is proposing this action because the existing test for Mycoplasma 
is restrictive in that it identifies only one test method in detail to 
be used even though other methods also may be appropriate. More 
sensitive and specific methods exist and are currently being practiced, 
and removal of the specific method to test for Mycoplasma provides 
flexibility for accommodating new and evolving technology and 
capabilities without

[[Page 12535]]

diminishing public health protections. This action is part of FDA's 
implementation of Executive Orders 13771 and 13777. Under these 
Executive orders, FDA is comprehensively reviewing existing regulations 
to identify opportunities for repeal, replacement, or modification that 
will result in meaningful burden reduction, while allowing the Agency 
to achieve our public health mission and fulfill statutory obligations.

DATES: Submit either electronic or written comments on the proposed 
rule by June 17, 2019.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before June 17, 2019. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of June 17, 2019. Comments received 
by mail/hand delivery/courier (for written/paper submissions) will be 
considered timely if they are postmarked or the delivery service 
acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2018-N-4757 for ``Revocation of the Test for Mycoplasma.'' Received 
comments, those filed in a timely manner (see ADDRESSES), will be 
placed in the docket and, except for those submitted as ``Confidential 
Submissions,'' publicly viewable at https://www.regulations.gov or at 
the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through 
Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Tami Belouin, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-
402-7911.

SUPPLEMENTARY INFORMATION: 

Table of Contents

I. Executive Summary
    A. Purpose of the Proposed Rule
    B. Summary of the Major Provisions of the Proposed Rule
    C. Legal Authority
    D. Costs and Benefits
II. Background
    A. Introduction
    B. Need for Regulation
III. Legal Authority
IV. Description of the Proposed Rule
    A. Scope
    B. Appropriate Controls Would Remain in Place
V. Proposed Effective Date
VI. Economic Analysis of Impacts
VII. Analysis of Environmental Impact
VIII. Paperwork Reduction Act of 1995
IX. Federalism
X. Consultation and Coordination with Indian Tribal Governments
XI. References

I. Executive Summary

A. Purpose of the Proposed Rule

    FDA proposes to remove the regulation requiring a specified test 
for the presence of Mycoplasma for live virus vaccines produced from in 
vitro living cell cultures and inactivated virus vaccines produced from 
such living cell cultures because the regulation is restrictive in that 
it identifies only one test method in detail to be used even though 
other methods also may be appropriate. More sensitive and specific 
methods exist and are currently being practiced, and removal of the 
required test for Mycoplasma provides flexibility for accommodating new 
and evolving technology and capabilities without diminishing public 
health protections.

B. Summary of the Major Provisions of the Proposed Rule

    The proposed rule removes Sec.  [thinsp]610.30 (21 CFR 610.30), 
which details the method for Mycoplasma testing of samples of the virus 
harvest pool and control fluid pool of live virus vaccines and 
inactivated virus vaccines produced from in vitro living cell cultures.

C. Legal Authority

    FDA is taking this action under the biological products provisions 
of the Public Health Service Act (the PHS Act), and the drugs and 
general

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administrative provisions of the Federal Food, Drug, and Cosmetic Act 
(FD&C Act).

D. Costs and Benefits

    Because this proposed rule would not impose any additional 
regulatory burdens, this regulation is not anticipated to result in any 
compliance costs and the economic impact is expected to be minimal.

II. Background

A. Introduction

    On February 24, 2017, Executive Order 13777, ``Enforcing the 
Regulatory Reform Agenda'' (https://www.federalregister.gov/documents/2017/03/01/2017-04107/enforcing-the-regulatory-reform-agenda, 82 FR 
12285; March 1, 2017) was issued. One of the provisions in the 
Executive order requires Agencies to evaluate existing regulations and 
make recommendations to the Agency head regarding their repeal, 
replacement, or modification, consistent with applicable law. As part 
of this initiative, FDA is proposing to revoke a regulation as 
specified in this proposed rule.

B. Need for Regulation

    It has become increasingly clear that the test for Mycoplasma 
requirements is too restrictive for live virus vaccines and inactivated 
virus vaccines produced from in vitro living cell cultures because they 
specify particular methodologies when alternatives may be available 
that provide the same or greater level of assurance of safety. 
Modifications to mycoplasma testing described in Sec.  610.30 must meet 
the requirements of 21 CFR 610.9.
    Thus, the Agency believes that the regulation may no longer reflect 
the current testing procedures as a general matter and that it is more 
appropriate, flexible, and efficient to identify appropriate testing 
requirements for particular products in the biologics license 
application (BLA).
    This proposed rule would remove the specified test for the presence 
of Mycoplasma to provide flexibility for accommodating new and evolving 
technology and capabilities without diminishing public health 
protections. Removal of this regulation would allow manufacturers of 
live virus vaccines produced from in vitro living cell cultures and 
inactivated virus vaccines produced from such living cell cultures to 
select the most scientifically appropriate Mycoplasma testing method to 
assure the safety, purity, and potency of their vaccines.
    These newer technologies can result in higher sensitivity and 
specificity of Mycoplasma detection and could reduce the time required 
to complete testing for Mycoplasma. Removal of this regulation would 
not remove Mycoplasma testing requirements specified in individual 
BLAs. A manufacturer of a live virus vaccine produced from in vitro 
living cell cultures and inactivated virus vaccines produced from such 
living cell cultures would continue to be required to follow the 
Mycoplasma test requirements specified in its BLA, unless the BLA were 
revised to modify or replace the test through a supplement in 
accordance with Sec.  [thinsp]601.12(c) (21 CFR 601.12(c)). FDA would 
review proposed changes to a manufacturer's approved biologics license 
in the context of that particular application to ensure that any such 
action is appropriate.
    The proposed rule, if finalized, will remove the regulation; 
however, a manufacturer would continue to be required to test for 
Mycoplasma as specified in its BLA. If finalized, this action will 
provide regulated industry with flexibility, as appropriate, to employ 
advances in science and technology as they become available, without 
diminishing public health protections. As appropriate, the Agency will 
describe the appropriate tests for particular products in 
manufacturers' BLAs.

III. Legal Authority

    FDA is issuing this proposed rule under the biological products 
provisions of the PHS Act (42 U.S.C. 216, 262, 263, 263a, and 264) and 
the drugs and general administrative provisions of the FD&C Act (21 
U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c, 360d, 360h, 360i, 371, 
372, 374, and 381). Under these provisions of the PHS Act and the FD&C 
Act, we have the authority to issue and enforce regulations designed to 
ensure that biological products are safe, pure, and potent, and prevent 
the introduction, transmission, and spread of communicable disease.

IV. Description of the Proposed Rule

A. Scope

    The test for Mycoplasma in Sec.  [thinsp]610.30 is intended to 
ensure that live virus vaccines produced from in vitro living cell 
cultures, and inactivated virus vaccines produced from such living cell 
cultures do not contain Mycoplasma. Currently the regulation details 
the method for Mycoplasma testing of samples of the virus harvest pool 
and control fluid pool of live virus vaccines and inactivated virus 
vaccines produced from in vitro living cell cultures. Removal of this 
regulation would eliminate a restrictive and duplicative requirement 
and accommodate new and evolving technology.
    We are proposing to remove the specified test for the presence of 
Mycoplasma for live virus vaccines produced from in vitro living cell 
cultures and inactivated virus vaccines produced from such living cell 
cultures. FDA is proposing this action because the existing specified 
test for the presence of Mycoplasma is restrictive and duplicative of 
requirements that are also specified in the BLA. This change is 
intended to remove restrictive or duplicative requirements and 
accommodate new and evolving technology and capabilities without 
diminishing public health protections. Removal of this regulation would 
not remove Mycoplasma testing requirements specified in individual 
BLAs. A biological product manufacturer would continue to be required 
to follow the Mycoplasma testing requirements specified in its BLA 
unless the BLA were revised to modify or replace the test through a 
supplement in accordance with Sec.  601.12(c). FDA would review 
proposed changes to a manufacturer's approved biologics license in the 
context of that particular license to ensure that any such action is 
appropriate.
    FDA is proposing to remove the requirements contained in Sec.  
[thinsp]610.30 from the regulations. As a result of removing Sec.  
[thinsp]610.30, we would also remove and reserve 21 CFR part 610, 
subpart D. FDA is proposing this action because the testing method 
described in the regulation is restrictive and more sensitive and 
specific testing methods are now available.

B. Appropriate Controls Would Remain in Place

    FDA believes that if this rulemaking becomes finalized as proposed, 
we would be able to continue to ensure that appropriate controls remain 
in place. If the proposed rule is finalized and the regulation calling 
for a specific test for Mycoplasma is eliminated, manufacturers would 
continue to be required to perform a test for Mycoplasma described in 
their BLAs for their licensed live virus vaccines produced from in 
vitro living cell cultures and their inactivated virus vaccines 
produced from such cultures. Such requirement would remain in effect 
unless the BLA were revised to modify or replace the test through a 
supplement in accordance with Sec.  [thinsp]601.12(c). FDA would review 
proposed changes to a manufacturer's approved biologics license in the 
context of that particular license to

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ensure that any such action is appropriate.

V. Proposed Effective Date

    FDA is proposing that any final rule based on this proposed rule 
become effective 30 days after the date of its publication in the 
Federal Register.

VI. Economic Analysis of Impacts

    We have examined the impacts of the proposed rule under Executive 
Order 12866, Executive Order 13563, Executive Order 13771, the 
Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded 
Mandates Reform Act of 1995 (Pub. L. 104-4). Executive Orders 12866 and 
13563 direct us to assess all costs and benefits of available 
regulatory alternatives and, when regulation is necessary, to select 
regulatory approaches that maximize net benefits (including potential 
economic, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). Executive Order 13771 
requires that the costs associated with significant new regulations 
``shall, to the extent permitted by law, be offset by the elimination 
of existing costs associated with at least two prior regulations.'' We 
believe that this proposed rule is not a significant regulatory action 
as defined by Executive Order 12866.
    The Regulatory Flexibility Act requires us to analyze regulatory 
options that would minimize any significant impact of a rule on small 
entities. Because this proposed rule would increase flexibility and 
does not add any new regulatory responsibilities, we propose to certify 
that the proposed rule will not have a significant economic impact on a 
substantial number of small entities.
    The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires 
us to prepare a written statement, which includes an assessment of 
anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $150 million, using the most current (2017) Implicit 
Price Deflator for the Gross Domestic Product. This proposed rule would 
not result in an expenditure in any year that meets or exceeds this 
amount.
    We believe industry will largely maintain their current practices 
following the removal of Sec.  610.30 Test for Mycoplasma. Although 
manufacturers of live virus vaccines and inactivated virus vaccines 
produced from in vitro living cell cultures may experience some 
unquantifiable cost savings from streamlining their testing procedures, 
we predict no quantifiable cost savings. FDA will also maintain its 
current practices, similarly generating no quantifiable cost savings. 
Therefore, we expect this proposed rule to be cost neutral.
    We have developed a comprehensive Preliminary Economic Analysis of 
Impacts that assesses the impacts of the proposed rule. The full 
preliminary analysis of economic impacts is available in the docket for 
this proposed rule and at https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

VII. Analysis of Environmental Impact

    We have determined under 21 CFR 25.31(h) that this action is of a 
type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

VIII. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed rule contains no 
collection of information. Therefore, clearance by the Office of 
Management and Budget under the Paperwork Reduction Act of 1995 is not 
required.

IX. Federalism

    We have analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. We have determined that 
this proposed rule does not contain policies that have substantial 
direct effects on the States, on the relationship between the National 
Government and the States, or on the distribution of power and 
responsibilities among the various levels of government. Accordingly, 
we conclude that the rule does not contain policies that have 
federalism implications as defined in the Executive order and, 
consequently, a federalism summary impact statement is not required.

X. Consultation and Coordination With Indian Tribal Governments

    We have analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13175. We have tentatively 
determined that the rule does not contain policies that would have 
substantial direct effects on one or more Indian tribes, on the 
relationship between the Federal Government and Indian tribes, or on 
the distribution of power and responsibilities between the Federal 
Government and Indian tribes. The Agency solicits comments from tribal 
officials on any potential impact on Indian Tribes from this proposed 
action.

XI. Reference

    The following reference is on display at the Dockets Management 
Staff (see ADDRESSES) and is available for viewing by interested 
persons between 9 a.m. and 4 p.m. Monday through Friday; it is also 
available electronically at https://www.regulations.gov. FDA has 
verified the website address, as of the date this document publishes in 
the Federal Register, but websites are subject to change over time.

1. FDA/Economics Staff, ``Elimination of 21 CFR 610.30 Test for 
Mycoplasma, Preliminary Regulatory Impact Analysis, Preliminary 
Regulatory Flexibility Analysis, Unfunded Mandates Reform Act 
Analysis,'' 2018. (Available at: https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.)

List of Subjects in 21 CFR Part 610

    Biologics, Labeling, Reporting and recordkeeping requirements.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and the 
Public Health Service Act, and under authority delegated to the 
Commissioner of Food and Drugs, it is proposed that 21 CFR part 610 be 
amended as follows:

PART 610--GENERAL BIOLOGICAL PRODUCTS STANDARDS

0
1. The authority citation for part 610 continues to read as follows:

    Authority:  21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c, 
360d, 360h, 360i, 371, 372, 374, 381; 42 U.S.C. 216, 262, 263, 263a, 
264.

Subpart D--[Removed and Reserved]

0
2. Remove and reserve subpart D, consisting of Sec.  610.30.

    Dated: March 26, 2018.
Scott Gottlieb,
Commissioner of Food and Drugs.
[FR Doc. 2019-06188 Filed 4-1-19; 8:45 am]
 BILLING CODE 4164-01-P